Objective To elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer(CRC)by using the two-sample and two-step Mendelian randomization(MR)methods,and to explore the mediating role and proportion of immune cells as intermediary factors.Methods The pooled statistical data related to the study were screened,and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method.Simultaneously,the causal effect was verified via Bayesian weighted MR.Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits.Sensitivity,heterogeneity,and pleiotropy analyses were performed to verify the reliability of the study results.Results The causal relationship between nine lipid traits and CRC was preliminarily identified,and no reverse causal effect was found(P>0.05).The validity of the results was verified via Bayesian weighted MR(P<0.05).Twenty-seven types of immune cells were suggested to exert a causal effect on CRC.The causal effect of phosphatidylcholine(O-18:2_20:4)on CRC was determined via mediation analysis(OR:0.8579,95% CI=0.7395-0.9952,P=0.0429).The CD127-mediated proportion on CD45RA+CD4+T cells was 9.14% (β=-0.1052,P=0.0155).Conclusion A causal relationship exists between lipid traits and CRC,and the intervention of CD127 on CD45RA+CD4+T cell helps phosph-atidylcholine reduce the risk of CRC.

Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Objective:To evaluate the effect of ozone preconditioning on splenic natural killer (NK) cells in septic mice.Methods:Twenty-four SPF-grade male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) according to the random number table method: control group (group C), lipopolysaccharide (LPS)group, ozone+ LPS group (O 3+ LPS) and air+ LPS group (Air+ LPS). The sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Ozone preconditioning was started at 5 days before developing the model: ozone 1 mg/kg was intraperitoneally injected once a day for 5 consecutive days, the equal volume of air was injected in Air+ LPS group. The survival was observed within 72 h after LPS injection, and sepsis score and ear temperature (once every 2 h, an average was calculated) were recorded. The posterior orbital venous blood samples were taken at 6 and 24 h after LPS injection for determination of serum interferon-γ (IFN-γ) and interleukin-10 (IL-10) concentrations using enzyme-linked immunosorbent assay. The spleen was then taken, and a single cell suspension of the spleen was prepared for measurement of the percentage of NK cells in the spleen by flow cytometry. Results:Compared with C group, the ear temperature, sepsis score and 72-h survival rate were significantly decreased, serum IFN-γ and IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was increased at 6 h after LPS injection and decreased at 24 h after LPS injection in LPS, Air+ LPS and O 3+ LPS groups ( P<0.05). Compared with LPS group, the ear temperature, sepsis score and 72-h survival rate were significantly increased, serum IFN-γ concentrations were decreased at each time point after LPS injection, serum IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was decreased at 6 h after LPS injection and increased at 24 h after LPS injection in O 3+ LPS group ( P<0.05), and no significant change was found in the parameters mentioned above in Air+ LPS group ( P>0.05). Conclusions:The mechanism by which ozone preconditioning reduces sepsis may be related to reduction of inflammatory responses and regulation of splenic NK cell levels in septic mice.

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

Objective:To investigate the value of net water uptake (NWU) in predicting malignant edema (ME) in large hemispheric infarction (LHI).Methods:Fifty-six patients suffering from LHI in the General Hospital of Northern Theater Command from September 2017 to July 2018 were retrospectively analyzed, and their NWU was calculated separately. Patients were divided into two groups according to the occurrence of ME, which was defined as space-occupying infarct requiring decompressive craniectomy or death resulting from cerebral hernia in seven days from onset. The clinical characteristics were analyzed, and receiver operating characteristic (ROC) curve and respective area under curve (AUC) were used to assess the value of NWU and other factors.Results:After adjusting for atrial fibrillation, National Institutes of Health Stroke Scale scores at admission, and time from onset to imaging, multivariable analysis showed that NWU was an independent predictor of ME ( OR=1.226，95% CI 1.040-1.446, P=0.015). According to the ROC curve, NWU≥13.08% identified ME with great predictive power (AUC=0.813;sensitivity 0.64, specificity 0.94). Conclusions:NWU is an important predictor of ME in patients with LHI. It can help identify patients at risk of ME.

OBJECTIVE： To investigate the potential pharmacological mechanism of the seed of Draba nemorosa， and to provide reference for further development， utilization and clinical application. METHODS： Effective components and related target proteins of D. nemorosa were screened and identified by using TCMSP and STRING database. Cytoscape 3.7.0 software was used to construct a visual network of effective components and target proteins for the seed of D. nemorosa， and the network topology analysis was performed. The targeting protein-protein interaction （PPI） network was constructed and analyzed by STRING database and Cytoscape 3.7.0 software. KEGG pathway enrichment of target proteins was analyzed by DAVID bioinformatics resource database. RESULTS： A total of 9 effective components were screened from the seed of D. nemorosa， including quercetin， kaempferol， β-sitosterol， etc. Totally 174 target proteins were obtained， mainly including PTGS2， NCOA2， PGR， etc. Among them， JUN and MAPK1 were core proteins in PPI network. KEGG enrichment pathway included PI3K/Akt signaling pathway， TNF-α signaling pathway， HIF-1 signaling pathway， Toll-like receptor signaling pathway and thyroid hormone signal pathway， etc. CONCLUSIONS： Effective components from the seed of D. nemorosa such as quercetin， kaempferol and β-sitosterol may act on PTGS2， JUN and MAPK1 target proteins through PI3K-Akt signaling pathway and TNF-α signaling pathway， thus exert the effects of purging lung， relieving asthma， promoting edema and reducing edema.

Silver nanoparticles were prepared by chemical reduction. Fusarium graminearum was used as the test strain. To study the inhibition of F. graminearum by silver nanoparticles, we studied the activities of protective enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the contents of osmotic adjustment substances soluble protein, soluble sugar and malonaldehyde (MDA) in F. graminearum. Silver nanoparticles inhibited F. graminearum and the inhibitory effect was increased with the concentration of silver nanoparticles. The inhibition rate of 10 μg/mL silver nanoparticles was more than 90% and EC50 was 0.59 μg/mL. When the treating time prolonged (2, 4, 6, 8 and 10 h), the activity of SOD, CAT and POD increased firstly and then declined. SOD, POD and CAT reached the maximum at 4 hours, and decreased to minimum at 10 hours. Silver nanoparticles also increased the MDA content and reduced the soluble sugar and protein contents in pathogens. These results indicated that cell integrity was destroyed in the presence of silver. This may be one of the inhibiting mechanisms of silver nanoparticles on the growth of F. graminearum.

Objective To measure the costs of primary health services in the community for developing government compensation standard and prediction of budget in 201 5.Methods Literature review and panel discussions were used to build the index database.A two-round Delphi expert consultation determined the work to do and steps for community healthcare standards.60 community health centers were sampled by stratified random sampling for survey,and the work hours,workload and service volume of respective services in 2013 were measured according to the service standards of primary care.Results The community primary care consists of the categories of outpatient services,nursing care, laboratory tests and drug management,totaling 20 services and 88 working procedures.The total work hours of primary healthcare service at 60 community health centers were 2 557 187.9 hours,which is adjusted to 2 959 21 5.1 hours based on workload coefficients.Based on the income standards of employees at the community health centers investigated,and the human cost price which was recommended by the experts,the total costs of primary healthcare of the 60 centers were 245 million,248 million and 318 million respectively,and the average cost was 71.0 yuan,71.8 yuan and 92.1 yuan per visit respectively.By such standards,the government should subsidize 38.9 ~ 60.0 yuan per visit to the centers.The total expenditure of primary healthcare of all communities in Shenzhen in 201 5 was predicted to be 314 to 407 million,for which the government is expected to subsidize 1.68~2.58 billion.Conclusion The subsidies for community primary healthcare fall short as the cost per visit runs up in 2013 to 71.0 yuan per visit or more,far above the current subsidy of 32.1 yuan per person.The subsidy per visit should be made 50.0 yuan in 201 5.